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402577 | New Interpretation | 01/22/2019 1:29 PM |
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Tier 2InterpretationPTEN is an obligate haplo-insufficient tumor suppressor gene and is mutated in a large number of cancers. It encodes a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/mTOR signaling pathway. Cancer-associated alterations in this gene often result in loss of PTEN protein and upregulation of the PI3K/AKT/mTOR pathway. PTEN mutations have been reported in 15% of anaplastic thyroid cancer. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome. Patients with Cowden syndrome have an increased risk of developing epithelial thyroid cancer, follicular carcinoma being the most common, of up to 10% compared to <1% in the general population. The PTEN I101T has been observed in a variety of cancer types. One study identified the PTEN I101T variant in 1 out of 172 patients with germ line PTEN mutations. Of note, an in vitro studied observed that the PTEN I101T variant reduced the half-life of PTEN as well as significantly reduced its activity. Clinical trials using PI3K-beta inhibitor are available for patients with PTEN-deficient tumors.
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- Landa I, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest 2016;126(3):1052-66
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- Pilarski R, Stephens JA, Noss R, Fisher JL, Prior TW. Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features. J Med Genet. 2011 Aug;48(8):505-12.
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Last updated: 2019-01-22 18:29:19 UTC
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